22-39134730-C-T

Variant names:

• chr22-39134730-C-T
• rs755050854
• NM_175709.5:c.269G>A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4 BS2

The NM_175709.5(CBX7):​c.269G>A​(p.Arg90Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000427 in 1,406,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000043 (0 hom.)
• Consequence: CBX7 NM_175709.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.77

Genes affected

CBX7 (HGNC:1557): (chromobox 7) This gene encodes a protein that contains the CHROMO (CHRomatin Organization MOdifier) domain. The encoded protein is a component of the Polycomb repressive complex 1 (PRC1), and is thought to control the lifespan of several normal human cells. [provided by RefSeq, Oct 2016]

ENSG00000279833 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.29304308).
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CBX7	NM_175709.5	c.269G>A	p.Arg90Gln	missense_variant	Exon 5 of 6	ENST00000216133.10	NP_783640.1
CBX7	NM_001346743.2	c.269G>A	p.Arg90Gln	missense_variant	Exon 5 of 6		NP_001333672.1
CBX7	NM_001346744.2	c.247-257G>A		intron_variant	Intron 4 of 5		NP_001333673.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CBX7	ENST00000216133.10	c.269G>A	p.Arg90Gln	missense_variant	Exon 5 of 6	1	NM_175709.5	ENSP00000216133.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000182 AC: 3 AN: 165122 Hom.: 0 AF XY: 0.0000111 AC XY: 1 AN XY: 90054

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000371

Gnomad ASJ exome AF: 0.000120

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000157

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000427 AC: 6 AN: 1406534 Hom.: 0 Cov.: 32 AF XY: 0.00000144 AC XY: 1 AN XY: 693478

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000261

Gnomad4 ASJ exome AF: 0.0000397

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000370

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000771 Hom.: 0

Bravo AF: 0.0000151

ExAC AF: 0.0000258 AC: 3

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.269G>A (p.R90Q) alteration is located in exon 5 (coding exon 5) of the CBX7 gene. This alteration results from a G to A substitution at nucleotide position 269, causing the arginine (R) at amino acid position 90 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.095	T;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.29	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-2.3	N;N
REVEL	Benign	0.20
Sift	Uncertain	0.011	D;D
Sift4G	Benign	0.12	T;.
Polyphen		1.0	D;.
Vest4		0.43
MVP		0.73
MPC		1.4
ClinPred		0.70	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Varity_R		0.22
gMVP		0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs755050854; hg19: chr22-39530735;